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Doug Dollemore

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Sep 16, 2020 10:00 AM

A trio of five-year NIH grants will support University of Utah Health scientists who are investigating the causes and potential treatments for congenital cardiovascular disease, the most common birth defect in the United States. Photo credit: Getty Images

The National Institutes of Health has awarded a trio of five-year grants totaling more than $12 million to a group of University of Utah Health scientists at the forefront of congenital heart disease (CHD) and arrhythmia research. The grants will support U of U Health efforts to unravel the interaction between genetic and maternal factors involved in the onset of CHD, as well as explore ways to improve treatment of newborn infants who have it.

“CHD is the number-one killer of infants in their first year of life,” says H. Joseph Yost, Ph.D., vice chairman of basic science research in the Department of Pediatrics at U of U Health. “These grants are a product of the multidisciplinary and collaborative spirit of our research team. They will allow us to seek out the causes of this devastating set of diseases and make strides toward better outcomes.”

CHD is the most common birth defect in the United States, occurring in about 1 in every 110 births, according to the Centers for Disease Control and Prevention.

Its defects, which are present at birth, can adversely affect the structure or function of the heart in many ways, Yost says. They vary in severity, ranging from mild (such as a small hole in the heart) to critical (such as missing or poorly formed parts of the heart). In addition, CHD can influence neurological development, leading to learning disabilities as a child grows older.

U of U Health has long been recognized for innovating new approaches to cardiac care, including CHD. Because CHD is a complex condition, the U of U Health team tackles the disease from multiple angles, combining the expertise of data scientists, genomics experts, clinicians, and population health scientists. 

The latest set of NIH grants include one renewal and two new ones. The renewal will support Utah Pediatric Cardiac Genomics Center’s (PCGC) effort to develop a tool based on artificial intelligence (AI,) which will allow scientists to scrutinize a nationwide set of electronic health records (EHRs). The process will help scientists better match particular genetic defects with specific recommendations for clinical care.

“AI analysis of EHRs might allow physicians treating children with CHD to better understand the clinical consequences of certain genetic variants,” says Martin Tristani-Firouzi, M.D., a clinician-scientist at U of U Health and Primary Children’s Hospital and the PCGC principal investigator, along with Yost and Mark Yandell, Ph.D. “As a result, they will be able to make more appropriate decisions about interventions and therapies.”

The five-year grant is supported by the National Heart, Lung and Blood Institute as part of its Bench-to-Bassinet consortia. The Utah PCGC is only one of four centers to receive these highly competitive grants, Yost says.

Tristani-Firouzi is also principal investigator for a new NIH-supported, four-year project that seeks to improve understanding of atrial fibrillation, a common type of arrhythmia that is associated with stroke and early cardiovascular death. Specifically, the researchers will examine a genetic mutation in a particular transcription factor that appears to lead to the onset of atrial fibrillation early in life.

Using genetic-editing techniques, the scientists will study the effects of this mutation in animal models such as zebrafish. They’ll also investigate differences in heart cell function in families that are susceptible to early-onset atrial fibrillation and those that are not. To do it, they will induce adult stem cells acquired from blood samples to transform into heart cells, which can then be studied in the lab. If successful, Tristani-Firouzi says this research could lead to better treatments for this condition.

Another five-year grant, led by Yost, Tristani-Firouzi, and Gabor Marth, D.Sc., supports efforts to create a cardiovascular development data resource center (CDDRC). The center will be home to a cloud-based data set available to investigators nationwide who are studying various aspects of CHD. The data set will include information from a large number of animal models. Collaborators Frameshift Genomics are also funded through this grant to expand their interactive, visual genomics tool, Mosaic, to be the interface through which investigators will access and explore this data.

“Investigators will be able to access the cloud to ask specific questions or compare data from one animal to another,” Yost says. “It will allow us to simultaneously track common threads in animals and humans that might reveal genetic mutations that lead to CHD heart defects.”

This article was updated on October 22, 2020 to include a collaboration with Frameshift Genomics.





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